title: FMNL1 promotes proliferation and migration of leukemia cells.
abstract: The human FMNL1 is expressed predominantly in hematopoietic cells and has been described previously as overexpressed in hematopoietic malignancies. However, it is not known whether FMNL1 contributes to leukemogenesis. Here, we investigate the FMNL1 function using two different human leukemia models: Namalwa and K562 cell lines. FMNL1 depletion reduced cell proliferation and colony formation in both leukemic cell types, as well as a decrease in the tumor growth of FMNL1-depleted Namalwa cell xenografts. In addition, there was a decrease in migration and in TEM in FMNL1-depleted Namalwa cells. FMNL1 endogenously associates with Rac1, and FMNL1 silencing resulted in an increased Rac1 activity. The reduced migration observed in FMNL1-depleted cells was restored by inhibiting Rac activity. Our results indicate that FMNL1 stimulates leukemia cell proliferation as well as migration. This suggests that FMNL1 contributes to leukemogenesis and could act in part through Rac1 regulation.
authors.affiliation: Department of Biological Sciences, Federal University of São Paulo, Diadema, São Paulo, Brazil. patricia.favaro@unifesp.br
authors.forename: Patricia
authors.initials: P
authors.lastname: Favaro
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
authors.forename: João Agostinho
authors.initials: JA
authors.lastname: Machado-Neto
authors.forename: Mariana
authors.initials: M
authors.lastname: Lazarini
authors.forename: Matheus Rodrigues
authors.initials: MR
authors.lastname: Lopes
authors.forename: João Kleber Novais
authors.initials: JK
authors.lastname: Pereira
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
authors.forename: Elvira
authors.initials: E
authors.lastname: Infante
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
authors.forename: Sara Teresinha Olalla
authors.initials: ST
authors.lastname: Saad
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology*; D000080865:Formins; D006801:Humans; D007938:Leukemia / Q000209:etiology / Q000473:pathology*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; C476204:FMNL1 protein, human; D000080865:Formins; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein
keywords: Rac1; cell motility; formins; leukemogenesis; transendothelial migration